How a Bengaluru lab is trying to fix the gene as therapy for hereditary health problems

As Narayana Nethralaya is fronting it, the focus is on ocular (eye) diseases, though Ghosh’s own area of work is in muscular dystrophy.Sowmya Aji | ET Bureau | April 23, 2016, 08:10 IST

LCA at this lab does not stand for Light Combat Aircraft but for Laber’s Congenital Amaurosis (an eye disorder that primarily affects the retina). Words like retinoblastoma, monogenic diseases, biomarkers, split gene vectors and genetic database are flung around casually as this lab and its backer, the Narayana Nethralaya Foundation, gear up for an outreach overdrive.

They want to make India catch up on 10 years of world research and application. "We are a decade behind the West in gene therapy," says Narayana Nethralaya Vice Chairman Dr Rohit Shetty. "We should have started it long ago. If we don’t do it now, it will be a disaster."

Narayana Nethralaya began talking about setting up a gene therapy lab in 2010 and did some initial work with Professor G Kumaramanickavel. Prohibitive costs, tough fundraising and lack of trained personnel hampered progress and it took wings only in 2013, with geneticist Arkasubhra Ghosh, a PhD holder in gene therapy from the University of Missouri-Columbia, heading it.

Ghosh, who chucked aside a "safe" job at the Institute of Molecular Biology in Singapore to live his dream of research leading to practical application, leads a team of 30 including graduate students at Gene Repairs, Regeneration in Ophthalmic Workstation (GROW), all hard at work at various aspects of genetic research.

"We want to make genetic drugs at one-tenth the cost of what is being made in the West. Our people should be able to afford it and that is possible only if we make it here," Ghosh says.

He is a man with a mission. He wants to tackle it all — genetic eye problems, diabetes, muscular dystrophy, cancers, brain tumours — by fixing the DNA. "I know how to do it and I want to do it here," Ghosh says. He holds the international patent for a pure genetic engineering process of splitting a gene into two, sending it in separate vectors "like a courier" to the affected cell and then sticking it together with what he calls some "cool glue".

This process is essential for any type of gene therapy for single gene diseases like muscular dsytrophy (a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion), Sturgardt disease (an inherited form of juvenile degeneration of the pigmented area near the centre of the retina that causes progressive vision loss) or cystic fibrosis (a genetic disorder that affects mostly the lungs but also the pancreas, liver, kidneys, and intestine).

The work at the lab, though, is not limited to single gene diseases. It is simultaneously progressing on various fronts. As Narayana Nethralaya, the premier eye hospital, is fronting it, the focus is on ocular (eye) diseases, though Ghosh’s own area of work is in muscular dystrophy.

"The eye is the most complex organ in the body, it has about 22 layers. It is also the area where gene therapy has already proved to be effective," he points out. Gene therapy for LCA has reached stage IV in clinical trials in the US and the UK.

The problem, as both Ghosh and Shetty state, is that India has not yet woken up to the potential in gene therapy. They point out that clinical trials for genetic disorders that are happening in the West are limited to their own citizens.

"At any given point in time, there are at least five lakh boys in India - one in every 3,500 boys born — with muscular dystrophy, whose families just have to watch them degenerate and die. There is no research here, no clinical trials are possible and none of the institutions doing it in the West will take them as subjects," Ghosh says, insisting it is high time India joined the picture.

With no specialist on the subject even in the top body, the Drugs Controller of India, Indian law, governments and the healthcare and education systems have a long way to go to catch up with the world.

Ghosh and Shetty are pushing the matter on every front, attending national and international conferences, holding discussions with bureaucrats, politicians, academicians and doctors on every possible occasion. Both policy and legal support is necessary, if gene therapy has to go the way it is in the West, they say.

Till that happens, though, GROW is trying to help in its own way. The staff has identified a drug, used in treatment of dry eyes, which their research has revealed will also cure Keratoconus (a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape). They want to do clinical trials for this. They are researching tears and "biomarkers" in them that can identify cancer, diabetes and cardiovascular diseases. They are researching how gene therapy can cure brain tumours, cancers and blindness due to diabetes.

The real difference that they are making right now is tagging all patients they test for genetic problems that could be cured by gene therapy.

Daily, they tag at least three people and have consulted with more than 700 in the past one year. Most patients come from Narayana Nethralaya, but others are referred by doctors across the country. The GROW staff have set up a genetic database and a Geneye clinic, where a doctor, a genetic counsellor and a scientist collaborate to help patients with genetic disorders.

Genetic testing is done at subsidised rates for all patients with congenital disorders referred to them by doctors. Ghosh’s wife, Anuprita, a scientist and genetic counsellor, does the entire coordination and tagging of patients, who could benefit from gene therapy anywhere in the world.

"A family from Surat has a son and daughter, very bright, both with congenital blindness. I found a doctor in the UK who is conducting gene therapy clinical trials on the very problem that they have. We have connected both of them up and are hoping that the doctor will accept these children for clinical trials and it works successfully," Anuprita says.

Besides this, she has trained a girl with a masters in biotechnology, who suffers from partial blindness, to work with her in the lab and that itself, she says, is very inspiring for patients who see her as functional and self-sufficient. "I hope her condition does not worsen and the gene therapy solution is found for her problem in time," she adds.

As Ghosh points out, the bio-clock is ticking and there needs to be sufficient "good" genes in the affected portion, if any therapy has to work. Scientists are working round-the-clock trying to find the gene solutions, but awareness and the legal framework have to catch up at blinding speed, if these have to reach those suffering in time, he adds.